Our overall objectives are to: (1) characterize the properties of antibodies to glomerular basement membrane (GBM) in sera and kidney eluates from experimental animals and nephritic patients. (In view of our recent findings antibodies to other renal basement membranes must be included); (2) determine the antigenic stimulus and the nature of the immunizing event in human anti-GBM antibody nephritis; (3) explore the role of adjuvants in experimental and human anti-GBM antibody nephritis; and (4) study the specificity and properties of human nephrotoxic and nephritogenic ("nephritis-inducing") antigens. A new experimentally induced tubulo-interstitial renal disease in guinea pigs has been developed. This model represents the first experimental auto-immune disease in guinea pigs which is caused by autoantibodies alone. Furthermore, it differs from other well established models in that mycobacteria-free adjuvant is sufficient in the induction of disease. In addition we are investigating the etiology and pathogenesis of a new spontaneous renal disease we have observed in guinea pigs.